A Phase 4 interventional study of Boostrix IPV infant acellular Pertussis and Boostrix IPV infant whole Pertussis in Pertussis, sponsored by London School of Hygiene and Tropical Medicine. Status unknown at 1 site in Gambia. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-03-16.
Sponsored by London School of Hygiene and Tropical Medicine · Phase 4, Interventional, and Prevention
Currently, there are two types of vaccines available against pertussis (whooping cough), an infectious disease of the respiratory tract that can be extremely serious in very young children.
Both have advantages and disadvantages: The acellular form (aP, mainly used in resource-rich countries) does not appear to offer as long lasting protection, but the whole cell vaccine (wP, mainly used in LMIC) appears to be generally more reactogenic. There is consensus that a "better pertussis vaccine" ought to be designed.
The GaPs trial is part of a series of clinical trials performed by the PERtussIS COrrelates of Protection Europe (PERISCOPE) Consortium, an EU-funded group of investigators which aims to generate knowledge on immune responses to pertussis. A better understanding of human biomarkers of protective immune responses to B. pertussis and its waning immunity is needed to accelerate the design and testing of new pertussis vaccines with a longer duration of protection.
This proposal describes the design and objectives of the clinical trial to be conducted in the Gambia, which is the only site in Africa involved in the consortium and involves the recruitment of 600 mother/infant pairs. Pregnant women will be randomised to receive either the usually recommended tetanus vaccination or a combination vaccine against whooping cough, diptheria, tetanus and polio. Their infants will receive either aP or wP as part of their EPI vaccines, and resulting immune responses will be characterized in detail up to the age of 9 months. The investigators will use immunological assays to investigate the functional humoral and cellular responses to pertussis in infants born to mothers who are randomized to receiving pertussis vaccine in pregnancy or not, and their infants who will receive either aP or wP vaccine.
Our research questions are:
Does vaccination against pertussis in pregnancy have impact on subsequent immune responses to pertussis vaccine and other EPI vaccines in the infants Does vaccination of infants with wP vaccine induce different levels and functionality of antibody and/or T cell responses than vaccination with aP vaccine What is the difference in innate and acquired immunity- as measured with novel systems vaccinology tools- between being vaccinated with wP versus aP?
The investigators are conducting a randomised, controlled, double-blinded, clinical vaccine trial in pregnant women combined with an open-label controlled Phase IV clinical vaccine trial in their infants.
The trial will examine the differences in immunity generated by aP compared with wP in infants at 5 and 9 months of age, and examine the impact of maternal antibodies on the immune response of infants receiving aP or wP vaccines at two, three and four months.
The investigators aim to address two key question: 1. If measures of immunity in infants given aP or wP differ by 5 and 9 months of age; and 2: If and- if so- how maternal pertussis antibodies affect the development and maintenance of immunity to Bordetella pertussis in infants.
Rationale for the trial:
Pertussis (whooping cough) is an infectious disease that can be very serious- particularly in young infants- but preventable through vaccination. There are two types of vaccines: acellular (aP) and whole cell (wP) vaccines, both extensively used worldwide. A clearer understanding of how these two different types of vaccines work is fundamental when considering adjustments or rethinking vaccination strategies and such knowledge will help the future development of new vaccines, given that some LMIC have already introduced aP but the current WHO recommendation still continues to recommend wP vaccine for those who have not yet switched.
Increases in the incidence of pertussis infection, including fatal cases in young infants, have been recently observed in many regions in the world, more likely associated with the use of aP vaccines. As a consequence, it is now recommended in several countries that women should receive aP vaccination in pregnancy so that their high levels of pertussis antibody which will be passed on via the placenta can protect their babies in early life, before the infants have received sufficient doses of pertussis vaccine themselves. However, it is currently unclear if and how maternal antibodies affect long-term immunity to pertussis in infants.
Unlike in the UK, where many women of childbearing age would have received aP vaccine in childhood, in The Gambia, all women would have been primed with wP vaccine as part of the NIP. Hence a study in this group of women is uniquely placed to assess if different priming regimens could have different quantitative and qualitative effects on transplacental antibody transfer for pertussis antibody, providing additional insights in comparison to parallel studies in Europe under the PERISCOPE consortium (PERtussIS COrrelates of Protection Europe).
A better understanding of human biomarkers of protective immune responses to B. pertussis, and its waning immunity is needed to accelerate the design and testing of new pertussis vaccines with a longer duration of protection.
Trial design:
The investigators will recruit 600 mother/infant pairs. Following informed consent, sensitisation and eligibility checks including antenatal ultrasound to date the pregnancy, pregnant women will be randomised to receive either Boostrix IPV (contains antigens against pertussis, tetanus, diphteria and polio)- a vaccine recommended for pregnant women in the UK and other countries where recent pertussis outbreaks have been observed, or the tetanus vaccine routinely recommended for women in LMIC.
Pre vaccination antibody titres will be measured in the women prior to vaccination between 28-34 week gestation and vaccine responses measured subsequently at the time of giving birth. Cord blood will be collected to measure transfer of maternal antibody. Infants will be grouped to receive either aP or wP at 2,3 and 4 months of age, in line with routine EPI programs. Blood samples will be collected from infants prior to vaccination and following doses of vaccines at specific intervals to measure innate and acquired immune responses and followed up until 9 months of age. Infants will be allocated to subgroups for blood tests so that no infant will have between 4 and max 5 episodes of blood sampling up to the age of 9 months.
Samples will be processed for quantitative and qualitative antibody, innate and acquired cellular immune responses. Where available, samples will be stored for further investigations using transcriptomic and epigenetic methodologies. Samples, results and data will be shared with the PERISCOPE consortium members.
290 studies on the registry are indexed under Whooping Cough; 23 are open to participants now.
This study's planned enrollment of 600 is above the median of 400 across 228 interventional studies indexed under Whooping Cough.
Browse Whooping Cough studies →London School of Hygiene and Tropical Medicine is the lead sponsor of 298 studies on the registry; 15 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
vaccination of the mother with Boostrix-IPV vaccine which includes the infant acellular pertussis
Biological: Boostrix IPV infant acellular Pertussis
vaccination of mother with Boostrix -IPV which includes infant whole cell pertussis
Biological: Boostrix IPV infant whole Pertussis
vaccination of mother with TT-which includes infant acellular pertussis
Biological: TT infant acellular Pertussis
vaccination of mother with T which includes infant whole cell pertussis
Biological: TT infant whole Pertussis
mother is randomized to receive Boostrix ® Polio (GSK) and infant acellular pertussis
mother is randomized to receive Boostrix ® Polio (GSK) and infant whole Pertussis
mother is randomised to receive Tetanus Toxoid and infant acellular Pertussis
mother is randomised to receive Tetanus Toxoid and infant whole Pertussis
PT specific antibody GMC
PT-specific antibody GMC at 20 weeks in infants vaccinated with aP versus wP
Time frame: 20 weeks
PT specific antibody GMC
PT-specific antibody GMC at 9 months in infants vaccinated with aP versus wP
Time frame: 9 months
PT specific antibody
PT-specific antibody GMC at 20 weeks and 9 months in infants vaccinated with aP versus wP following maternal vaccination with Boostrix ® Polio (GSK) or Tetanus Toxoid.
Time frame: at 20 weeks and 9 months
change in PT, FHA, and PRN antibody concentrations
Proportion with a 2-fold reduction in PT, FHA, and PRN antibody concentrations (measured in cord blood) from baseline at 8, 20 weeks and 9 months of age in aP versus wP primed infants following maternal immunisation with Boostrix ® Polio (GSK) or Tetanus Toxoid
Time frame: at 8 and 20 weeks and at 9 months of age
Pertussis antigen-specific memory B-cell
Pertussis antigen-specific memory B-cell frequencies at 8,16 weeks and 9 months of age measured by ELISpot in the aP versus wP group following maternal immunisation with aP or Boostrix ® Polio (GSK) or Tetanus Toxoid
Time frame: at 8, 16 weeks and at 9 months of age
Pertussis antigen-specific Th1, Th2 and Th17 responses
Pertussis antigen-specific Th1, Th2 and Th17 responses determined by flow-cytometry and cytokine analysis following antigen-specific culture (the 'Rapid T-cell assay').
Time frame: at 16 weeks of age of the infant
PT, FHA and PRN-specific antibody GMC and GMR
PT, FHA and PRN-specific antibody GMC and GMR prior to immunisation (cord blood baseline) and at 8, 20 weeks and 9 months of age.
Time frame: at baseline (cord blood baseline) and at 8, 20 weeks and at 9 months
Hib, diphtheria, tetanus, pneumococcal and polio-specific antibody
Hib, diphtheria, tetanus, pneumococcal and polio-specific antibody concentrations
Time frame: at 8, 20 weeks and 9 months
Serious adverse events (SAE) in expectant mothers
Serious adverse events (SAE) in expectant mothers from enrollment at 28-34 weeks gestation up to eight weeks from the end of pregnancy.
Time frame: at 28-34 weeks gestation up to eight weeks from the end of pregnancy.
local and systemic reactogenicity
Proportion of mothers 28-34 weeks gestation with local and systemic reactogenicity within the first three days of aP administration
Time frame: within first 3 days of aP administration
PT specific antibody
PT-specific antibody GMC 9 months post delivery
Time frame: at 9 months post delivery
Started Jan 2019 (actual). Primary completion is estimated for May 2022, 39 months after the start.
Of 22 phase 4 interventional studies under Whooping Cough, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 34. This study's planned 39 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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